Old and novel surfactant protein C (SP-C) mutations in children

Genetic variations of SP-C gene are known to cause interstitial lung disease. In previous studies 55 patients have been described focussing on the genetic abnormalities and clinical course. Here we report the data of children with SP-C mutations collected between 1998 and 2010. Lung biopsy findings and previous radiological imaging studies were re-examined using up to date classifications. All 11 children identified had heterozygous mutations in the SP-C gene, six of which carried I73T and five other mutations (H59R, G74V, C121F, E191X, A112T). Age at onset of symptoms ranged from birth to 11 years; however most presented with postnatal respiratory distress syndrome or later with tachypnea, cough and failure to thrive. Chest computer tomography showed a variety of different patterns including ground glass attenuation, mosaic pattern, lung fibrosis and cysts. Initial diagnosis was made by genetic testing alone in 6 of 11 cases and by lung biopsy in 5 patients. Histology pattern included non specific interstitial pneumonia and desquamative interstitial pneumonia, chronic pneumonitis of infancy, pulmonary alveolar proteinosis and end stage fibrosis. Average follow-up was 7.1 years (0.8-18.8), disease progression ameliorated in 6 and remained unchanged in 5 children. During infancy treatments given included corticosteroids and hydroxychloroquine with mixed results. Currently 2 children do not require medical treatment. The manifestation of interstitial lung disease due to SP-C mutations is variable, however many children present during neonatal period and infancy. Intermediate term course seems favourable. Efficacy of empirical treatments urgently needs to be assessed in randomized trial.